Our research interests are to elucidate the molecular mechanisms of aging and their roles in the development and treatment of age-related disease. Specifically, our lab has discovered a novel enzyme called Pin1 that is able to control protein structure after phosphorylation, thereby introducing a new signaling mechanism to regulate diverse cellular processes. More importantly, we have shown that deregulation of Pin1 plays a pivotal role in the development of aging and age-related disease, notably cancer and Alzheimer's disease, with Pin1 being an attractive new drug target. In addition, our lab has identified several new proteins important for maintaining telomere structures, including PinX1, a conserved and potent telomerase inhibitor and a new tumor suppressor that has a major impact on the development of many common human cancers.
Zhou, X.Z. and Lu, K.P. 2001, The Pin2/TRF1-interacting protein PinX1 is a potent telomerase inhibitor. Cell 107: 347-359
Liou, Y.-C., Sun, A., Ryo, A., Zhou, X. Z., Yu, Z.-X., Huang, H.-K., Bronson, R., Uchida, T., Bing, G., Li, X., Hunter, T. and Lu, K. P. 2003, Role of the prolyl isomerase Pin1 in protecting against age-dependent neurodegeneration. Nature 424: 556-561.
Pastorino, L., Sun, A., Lu, P. J., Zhou, X. Z., Balastik, M., Finn, G., Wulf, G., Lim, J., Li, S. H., Li, X., Xia, W., Nicholson, L. and Lu, K. P. 2006, The prolyl isomerase Pin1 regulates amyloid precursor protein processing and Amyloid-beta production. Nature 440: 528-534.
Lim, J., Balastik, M., Lee, T. H. Liou, Y. C., Sun, A., Finn, G., Pastorino, L. Lee, V. M.-Y. and Lu, K. P. 2008, Pin1 has opposite effects on wild-type and P301L tau stability and tauopathy. J. Clin. Invest. 118: 1877-1889 (Highlighted “In this Issue” J. Clin. Invest. 118: 1585.
Lee, T. H., Lim, J., Tun-Kyi, A., Finn, G., Shi, R., Balastik, M., Pastorino, L., Wulf, Zhou, X. Z. and Lu, K. P. 2008, Essential role of the phosphorylation specific isomerase Pin1 in regulating TRF1 protein stability, telomere maintenance and aging. Nature Cell Biol (in press).
External Recognition:
1993-1994 National Institutes of Health Fellow
1995-1996 Leukemia Society of America Fellow
1998-2003 Leukemia and Lymphoma Society Scholar
1999 Young Investigator Award, The Society of Chinese Bioscientists in America
1999-2003 Pew Scholar in Biomedical Sciences
2004-present Member, NIA-N (Neuroscience of Aging) Review Committee, NIH
2007-present Editorial Board Member, Molecular and Cellular Biology
2007-present Elected Member of American Society for Clinical Investigation
2007-2010 Sandler Program for Asthma Research Senior Investigator Award
2008 Honorary Master’s Degree, Harvard Medical School, Harvard University
Major Collaborative Activities:
A number of ongoing collaborations with faculty members at BIDMC and other Harvard Affiliates, including Drs. Lew Cantley, Lew Lipstiz, David Sinclair, Dirk Inglehart, Dennis Selkoe, and Dan Tenen.
